Pain-suppressive effects on various nociceptive stimuli (thermal, chemical, electrical and inflammatory) of the first orally active enkephalin-metabolizing enzyme inhibitor RB 120

@article{Noble1997PainsuppressiveEO,
  title={Pain-suppressive effects on various nociceptive stimuli (thermal, chemical, electrical and inflammatory) of the first orally active enkephalin-metabolizing enzyme inhibitor RB 120},
  author={Florence Noble and Claire Smadja and Olga Valverde and Rafael Maldonado and Pascale Coric and Serge Turcaud and Marie Claude Fourni{\'e}-Zaluski and B. Roques},
  journal={Pain},
  year={1997},
  volume={73},
  pages={383-391}
}
Enhancement of the effects of a complete inhibitor of enkephalin‐catabolizing enzymes, RB 101, by a cholecystokinin‐B receptor antagonist in diabetic rats
TLDR
It is demonstrated that the antinociception generated by RB’101, induced by elevation of extracellular levels of endogenous enkephalins, can be extended to neuropathic pain in diabetic rats and that blockade of CCK‐B receptors potentiated ant inociceptive effects elicited byRB’ 101.
Long-lasting oral analgesic effects of N-protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain
TLDR
In all tested models, the most efficient prodrug 2a (PL265) was active, at least during 150–180 min, after single oral administration of 2a, the active drug is the only generated metabolite produced, and these encouraging results have made 2a a suitable candidate for clinical development.
Modulation of disul fi de dual ENKephalinase inhibitors ( DENKIs ) activity by a transient N-protection for pain alleviation by oral route Herv
TLDR
DENKIs are able to relieve pain at its source thanks to the increase of enkephalin levels, and are shown to be highly efficient in peripherally-controlled inflammatory and neuropathic pain with long lasting effects but completely inactive in the acute centrally-controlled hot plate test, a model of pain by excess of nociception.
New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment.
TLDR
The design and synthesis of new pro-drugs, derived from co- drugs combining a NEP and an APN inhibitor through a disulfide bond with side chains improving oral bioavailability are reported, including 19-IIIa, a new DENKIs selected for clinical development.
A Novel Pregabalin Functionalized Salicylaldehyde Derivative Afforded Prospective Pain, Inflammation, and Pyrexia Alleviating Propensities
TLDR
The findings suggest that the synthesized compound possessed prospective pain, inflammation, and pyrexia relieving propensities and therefore may serve as a potential drug candidate for the therapeutic management of chronic pain conditions.
RB101-mediated protection of endogenous opioids: potential therapeutic utility?
TLDR
Findings suggest that RB101 and other inhibitors of enkephalin-degrading enzymes may have potential as novel therapeutic compounds for the treatment of pain, depression, and anxiety.
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References

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Inhibition of the enkephalin-metabolizing enzymes by the first systemically active mixed inhibitor prodrug RB 101 induces potent analgesic responses in mice and rats.
TLDR
The preferential involvement of mu opioid receptors in the analgesic effects of endogenous enkephalins, whose extracellular levels are increased by the two RB101-generated inhibitors, is suggested.
The Dual Peptidase Inhibitor RB101 Induces a Long‐Lasting Increase in the Extracellular Level of Met‐Enkephalin‐Like Material in the Nucleus Accumbens of Freely Moving Rats
TLDR
Data from this study represent the first direct evidence that dual inhibitors of enkephalin‐degrading enzymes increase in vivo the extracellular levels of Met‐enkephaline‐like material in awake and freely moving rats.
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